| Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. | |
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MedLine Citation:
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PMID: 2442255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present study shows the in vitro effects of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA). FK506 inhibited concanavalin A response and allo-mixed lymphocyte reaction of murine splenic lymphocytes in a dose-dependent manner, and at 40- to 200-fold lower concentrations than CsA. Allo-cytolytic T lymphocyte induction from murine thymocytes was also inhibited by FK506, whereas the ability of cytolytic T lymphocyte to lyse targets was not affected by the agent. Immunosuppressive effects of FK506 were further characterized by using antigen specific-proliferative T lymphocyte clones, BC.21 and KO.6. FK506 inhibited the proliferation of T cell clones stimulated with specific antigens in a dose-dependent manner, and at about 100-fold lower concentrations than CsA. However, cloned T cells, once activated, were scarcely affected by the agent; interleukin-2 (IL-2) driven proliferation of cloned T cells was not inhibited. On the other hand, it was found that FK506 inhibited both IL-2 secretion and IL-2 receptor expression of BC.21 after stimulation with the specific antigen. FK506 also inhibited the proliferation of BC.21 stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore, indicating that it directly affected the signaling pathway downward from the perturbation of the Ti/T3 complex. Finally, it was suggested that FK506 and CsA synergistically inhibited the antigen-driven proliferation of cloned T cells. These results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations. |
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Authors:
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S Sawada; G Suzuki; Y Kawase; F Takaku |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 139 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1987 Sep |
Date Detail:
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Created Date: 1987-10-15 Completed Date: 1987-10-15 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1797-803 Citation Subset: AIM; IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens Calcimycin / pharmacology Cell Line Concanavalin A / pharmacology Cyclosporins / pharmacology Drug Synergism Immunosuppressive Agents / pharmacology* Interleukin-2 / secretion Isoantigens Lymphocyte Activation / drug effects* Mice Pyridines / pharmacology Receptors, Immunologic / metabolism Receptors, Interleukin-2 T-Lymphocytes / drug effects* T-Lymphocytes, Cytotoxic / immunology Tacrolimus Tetradecanoylphorbol Acetate / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antigens; 0/Cyclosporins; 0/Immunosuppressive Agents; 0/Interleukin-2; 0/Isoantigens; 0/Pyridines; 0/Receptors, Immunologic; 0/Receptors, Interleukin-2; 109581-93-3/Tacrolimus; 11028-71-0/Concanavalin A; 16561-29-8/Tetradecanoylphorbol Acetate; 52665-69-7/Calcimycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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